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Open AccessArticle

Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions

1
CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal
2
Polytechnic of Coimbra, Coimbra Agriculture School, Bencanta, 3045-601 Coimbra, Portugal
3
Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland
*
Author to whom correspondence should be addressed.
Animals 2021, 11(1), 208; https://doi.org/10.3390/ani11010208
Received: 23 November 2020 / Revised: 21 December 2020 / Accepted: 14 January 2021 / Published: 16 January 2021
(This article belongs to the Special Issue Endometritis and Fibrosis: An Evolving Story)
Myeloperoxidase, which is released by neutrophils when they form neutrophil extracellular traps, has already been related to equine endometrosis development. The myeloperoxidase inhibitor 4-aminobenzoic acid hydrazide (ABAH) has shown promising results inhibiting myeloperoxidase in other pathological conditions. The metallopeptidases (MMP-2/-9) regulates the extracellular matrix turnover. In the present study, in equine explants from follicular phase, myeloperoxidase treatment increased collagen type I relative protein abundance, but the use of ABAH reduced it. In mid-luteal phase endometrial explants, MMP-2 seems to be implicated in an acute reaction to myeloperoxidase treatment, while in the follicular phase, MMP-9 might be associated with a prolonged exposition to myeloperoxidase. The impairment of equine endometrosis can be achieved by inhibiting the pro-fibrotic effects of myeloperoxidase using the inhibitor ABAH.
Neutrophils can originate neutrophil extracellular traps (NETs). Myeloperoxidase (MPO) is a peroxidase found in NETs associated to equine endometrosis and can be inhibited by 4-aminobenzoic acid hydrazide (ABAH). Metallopeptidases (MMPs) participate in extracellular matrix stability and fibrosis development. The objectives of this in vitro work were to investigate, in explants of mare’s endometrium, (i) the ABAH capacity to inhibit MPO-induced collagen type I (COL1) expression; and (ii) the action of MPO and ABAH on the expression and gelatinolytic activity of MMP-2/-9. Explants retrieved from the endometrium of mares in follicular or mid-luteal phases were treated with MPO, ABAH, or their combination, for 24 or 48 h. The qPCR analysis measured the transcription of COL1A2, MMP2, and MMP9. Western blot and zymography were performed to evaluate COL1 protein relative abundance and gelatinolytic activity of MMP-2/-9, respectively. Myeloperoxidase elevated COL1 relative protein abundance at both treatment times in follicular phase (p < 0.05). The capacity of ABAH to inhibit MPO-induced COL1 was detected in follicular phase at 48 h (p < 0.05). The gelatinolytic activity of activated MMP-2 augmented in mid-luteal phase at 24 h after MPO treatment, but it was reduced with MPO+ABAH treatment. The activity of MMP-9 active form augmented in MPO-treated explants. However, this effect was inhibited by ABAH in the follicular phase at 48 h (p < 0.05). By inhibiting the pro-fibrotic effects of MPO, it might be possible to reduce the development of endometrosis. Metallopeptidase-2 might be involved in an acute response to MPO in the mid-luteal phase, while MMP-9 might be implicated in a prolonged exposition to MPO in the follicular phase. View Full-Text
Keywords: endometrosis; myeloperoxidase; 4-aminobenzoic acid hydrazide; fibrosis; metallopeptidases endometrosis; myeloperoxidase; 4-aminobenzoic acid hydrazide; fibrosis; metallopeptidases
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MDPI and ACS Style

Amaral, A.; Fernandes, C.; Rebordão, M.R.; Szóstek-Mioduchowska, A.; Lukasik, K.; Pinto-Bravo, P.; Telo da Gama, L.; Jan Skarzynski, D.; Ferreira-Dias, G. Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions. Animals 2021, 11, 208. https://doi.org/10.3390/ani11010208

AMA Style

Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Pinto-Bravo P, Telo da Gama L, Jan Skarzynski D, Ferreira-Dias G. Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions. Animals. 2021; 11(1):208. https://doi.org/10.3390/ani11010208

Chicago/Turabian Style

Amaral, Ana; Fernandes, Carina; Rebordão, Maria R.; Szóstek-Mioduchowska, Anna; Lukasik, Karolina; Pinto-Bravo, Pedro; Telo da Gama, Luís; Jan Skarzynski, Dariusz; Ferreira-Dias, Graça. 2021. "Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions" Animals 11, no. 1: 208. https://doi.org/10.3390/ani11010208

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